title: Synthesis and antibacterial activities of N-substituted-glycinyl 1H-1,2,3-triazolyl oxazolidinones.
abstract: A series of 1H-1,2,3-triazolyl piperazino oxazolidinone analogs with optionally varied glycinyl substitutions were synthesized and their antibacterial activity assessed against a panel of susceptible and resistant Gram-positive and selected Gram-negative bacteria including clinical isolates. The N-aroyl- and N-heteroaroyl-glycinyl (MIC: 0.06-4 μg/ml) derivatives were more potent than the N-acylglycinyl (2-8 μg/ml) derivatives against all Gram-positive bacteria tested. Nitro substitution on aryl and heteroaryl rings significantly enhanced activity against Gram-positive bacteria, as noted with the 3,5-dinitrobenzoyl (6m and 6n) and 5-nitro-2-furoyl (6u and 6v) derivatives with MIC ranges of and 0.25-0.5 and 0.06-0.5 μg/ml, respectively. These nitro analogs also showed more potent extended activity against Moraxella catarrhalis, with MICs ranges of 0.25-1 μg/ml, compared to linezolid (MIC: 8 μg/ml). Hence, the presence of the N-aroyl and/or N-heteroaroyl glycinyl structural motifs as spacer group could significantly enhance the antibacterial activities of 1H-1,2,3-triazolyl oxazolidinone class of compounds.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kuwait University, PO Box 24923, Safat 13110, Kuwait. dphillips@hsc.edu.kw
authors.forename: Oludotun A
authors.initials: OA
authors.lastname: Phillips
authors.forename: Edet E
authors.initials: EE
authors.lastname: Udo
authors.forename: Mohammed E
authors.initials: ME
authors.lastname: Abdel-Hamid
authors.forename: Reny
authors.initials: R
authors.lastname: Varghese
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D018432:Drug Resistance, Multiple / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D023303:Oxazolidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D023303:Oxazolidinones
keywords: Antibacterial activity; Gram-positive bacteria; Linezolid; Substituted-glycinyl oxazolidinone; Triazolyl-oxazolidinone